Title

Estradiol Enhances Calcium Signaling by Excitatory GABA in Neonatal Hypothalamic Neurons: A Potential Mechanism for Sexual Differentiation

Document Type

Article

Publication Date

2001

Version

Publisher's PDF

Publication Title

Endocrinology

Keywords

GABA, estradiol, brain development

Subject Categories

Biology

Abstract

Contrary to the situation in adulthood, gammabutyric acid(GABA)A receptor activation during early brain development depolarizes neurons to open L-type voltage-gated Ca2+ channels. Because GABA is excitatory during the sensitive period of steroid-mediated brain sexual differentiation, we investigated whether estradiol modulates excitatory GABA during this period, by examining two parameters: 1) magnitude of GABA-induced calcium transients; and 2) developmental duration of excitatory GABA. Dissociated hypothalamic neurons from embryonic-day-15 rat embryos were loaded with the Ca2+ indicator, fura-2, and transient rises in [Ca2+]i(Ca2+ transient) were measured after application of 10 mM muscimol,a GABAA receptor agonist. Cells were treated with 10210 M estradiol or vehicle from 0–3 days in vitro (DIV) and imaged on 4 DIV, whereas others were treated from 3–6 DIV and imaged on 7 DIV. The mean amplitude of Ca2+ transients after muscimol administration were 68% and 61% higher in estradiol-treated neurons on 4 DIV and 7 DIV, respectively, relative to controls. Consistent with GABA becoming inhibitory in mature neurons, 50% fewer control neurons responded on DIV 7, relative to DIV 4. However, estradiol treatment maintained excitatory GABA on DIV 7 (72% in estradiol-treated vs. 35% in control). This is the first report of hormonal modulation of excitatory GABA, and it suggests that estradiol may mediate sexual differentiation by enhancing GABA induced increases in intracellular Ca2+.

Comments

Copyright 2001 Endocrinology. The original publication is available at Endocrinology.